Article
Biochemistry & Molecular Biology
Maryam Alhumaidi, Lea-Marie Nentwig, Hadiar Rahman, Lutz Schmitt, Andrew Rudrow, Andrzej Harris, Cierra Dillon, Lucas Restrepo, Erwin Lamping, Nidhi Arya, Suresh V. Ambudkar, John S. Choy, John Golin
Summary: In this study, the structure-function relationship of the conserved gates and gating regions in ABC multidrug transporters was investigated. The findings reveal that the gating region residues not only play a role in molecular gating but also in allosteric regulation, conformational switching, and protein folding.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Han- Yeh, Ying-Chun Yu, Pei-Lun Kuo, Chun-Kuang Tsai, Hsin-Tuan Huang, Tzyh-Chang Hwang
Summary: The opening of CFTR channel is related to the movement of nucleotide-binding domains, with active ATP hydrolysis triggering channel closure. The stable ATP binding in site 1 is crucial for CFTR's functional stability, and small molecules targeting site 1 may have therapeutic potential for addressing membrane instability in F508del-CFTR.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Biochemistry & Molecular Biology
Maria G. Khrenova, Egor S. Bulavko, Fedor D. Mulashkin, Alexander Nemukhin
Summary: The results of studying the GTP hydrolysis reaction mechanism using QM/MM MD simulations show the crucial role of the catalytic glutamine side chain. Two distinct pathways, pathway-I and pathway-II, were identified, with pathway-I explaining the impact of the Glu138Gly mutation in RP2 on slowing down the hydrolysis rate, while pathway-II aligns more closely with experimental kinetic data of the wild-type Arl3-RP2 complex.
Article
Biology
Norifumi Yamamoto, Genichi Sampei, Gota Kawai
Summary: In this study, a computational protocol was developed to analyze the free-energy profile for the glycine phosphorylation process catalyzed by PurD. Further analysis revealed that the partial atomic charge distribution within the substrate molecules was overall delocalized during the formation of glycyl-phosphate.
Article
Multidisciplinary Sciences
Yusuke Kanematsu, Akihiro Narita, Toshiro Oda, Ryotaro Koike, Motonori Ota, Yu Takano, Kei Moritsugu, Ikuko Fujiwara, Kotaro Tanaka, Hideyuki Komatsu, Takayuki Nagae, Nobuhisa Watanabe, Mitsusada Iwasa, Yuichiro Maeda, Shuichi Takeda
Summary: This study reveals the reaction mechanism of ATP hydrolysis by actin. Through structural analysis and calculations, the researchers have identified a specific reaction path, explaining the slow rate and irreversibility of actin ATP hydrolysis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Liga Skarda, Julia Kowal, Kaspar P. Locher
Summary: ABCG1 is an ATP binding cassette transporter that removes excess cholesterol from peripheral tissues, and its mechanism of cholesterol transport is still unknown. Structural comparisons reveal differences in mechanism and substrate specificity between ABCG1, ABCG2, and ABCG5/G8, providing insights into ABCG1-mediated cholesterol transport.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Medicinal
Biebele Abel, Megumi Murakami, Dilip K. K. Tosh, Jinha Yu, Sabrina Lusvarghi, Ryan G. G. Campbell, Zhan-Guo Gao, Kenneth A. A. Jacobson, Suresh V. Ambudkar
Summary: Various adenosine receptor nucleoside-like ligands were found to modulate ATP hydrolysis by the multidrug transporter ABCG2. Structure-activity analysis showed a separation of adenosine receptor and ABCG2 activities. Among them, adenine 37c and (N)-meth-anocarba 7-deaza-5'-ethyl ester 60 were potent stimulators of ABCG2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daniel Mann, Kristin Labudda, Sophie Zimmermann, Kai Ulrich Vocke, Raphael Gasper, Carsten Koetting, Eckhard Hofmann
Summary: This study presents time-resolved FTIR spectroscopic measurements of ATP binding and hydrolysis reaction in full-length MsbA. The reaction rates were determined and the study paves the way for investigations of allocrite transport in full-length MsbA using FTIR spectroscopy.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shunya Suenaga, Yu Takano, Toru Saito
Summary: A quantum mechanics/molecular mechanics molecular dynamics (QM/MM MD) study was conducted on three representative competitive inhibitors of urease. The study found that N-(n-butyl)phosphorictriamide (NBPTO) exhibited the highest inhibitory activity and the lowest IC50 value, followed by acetohydroxamic acid (AHA) and hydroxyurea (HU). The structural and thermodynamical properties of the inhibitors were found to be correlated with their inhibition efficiency.
Article
Biochemistry & Molecular Biology
Qingshan Luo, Huigang Shi, Xueqing Xu
Summary: Lipopolysaccharide (LPS) is a crucial component of the outer membrane in most Gram-negative bacteria, and its transport from the inner membrane to the outer membrane is facilitated by seven lipopolysaccharide transport proteins. This study presents the cryo-EM structures of LptB(2)FG and LptB(2)FGC from Klebsiella pneumoniae, highlighting the detailed interactions between LPS and the transporter.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sabrina Lusvarghi, Stewart R. Durell, Suresh V. Ambudkar
Summary: This study demonstrates that the ATP hydrolysis-defective mutant does not follow the same steps as the wild-type P-gp. The conformational differences in the EQ mutant may provide insights into the catalytic cycle of P-gp, suggesting the need for additional structural studies with the wild-type protein.
Article
Multidisciplinary Sciences
Zhaoxi Sun, Zhirong Liu
Summary: The study explores indirect free energy simulation methods at quantum mechanics and molecular mechanics levels, as well as attempts to optimize multi-scale treatment by changing the region for electronic structure calculations. The numerical tests show that the estimates from the indirect nonequilibrium perturbation framework are almost identical to the direct results, while the indirect equilibrium estimates deviate from the direct references.
ADVANCED THEORY AND SIMULATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jingxi Liang, Xiuna Yang, Tianyu Hu, Yan Gao, Qi Yang, Haitao Yang, Wei Peng, Xiaoting Zhou, Luke W. Guddat, Bing Zhang, Zihe Rao, Fengjiang Liu
Summary: This study used single particle cryo-electron microscopy (cryo-EM) to determine the structure of the trehalose-specific transporter in Mycobacterium tuberculosis and demonstrated the potential of this technique in exploring dynamic structures of transporters. It provides insights into the trehalose recycling mechanism in Mycobacterium tuberculosis.
Article
Biochemical Research Methods
Ryuichi Hirota, Zen-ichiro Katsuura, Naoki Momokawa, Hiroki Murakami, Satoru Watanabe, Takenori Ishida, Takeshi Ikeda, Hisakage Funabashi, Akio Kuroda
Summary: In this study, it was found that under specific conditions, a phosphite-dependent strain of Escherichia coli can generate escape mutants. The mutation occurs at position 210 of the transmembrane domain protein HtxC of the phosphorus compound transporter HtxBCDE. The replacement of a specific amino acid residue at this position can reduce the rate of escape mutant generation.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Mengmeng Wang, Jing-Xiang Wu, Lei Chen
Summary: Mitiglinide is a drug used for treating diabetes that works by inhibiting pancreatic channels to promote insulin secretion. Research has found that mitiglinide binds to a specific insulin secretagogue-binding site, locking it in a specific conformation and resulting in high selectivity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Physical
Donglian Huang, Shanfeng Chen, Jingzhi Pu, Xuecai Tan, Yan Zhou
JOURNAL OF PHYSICAL CHEMISTRY A
(2019)
Article
Instruments & Instrumentation
Courtney A. Cruse, Jingzhi Pu, John Goodpaster
APPLIED SPECTROSCOPY
(2020)
Article
Chemistry, Physical
Xiaoliang Pan, Junjie Yang, Richard Van, Evgeny Epifanovsky, Junming Ho, Jing Huang, Jingzhi Pu, Ye Mei, Kwangho Nam, Yihan Shao
Summary: This study presents a protocol for machine-learning-assisted free energy simulation of solution-phase and enzyme reactions at the ab initio quantum-mechanical/molecular-mechanical (ai-QM/MM) level. The developed MLP and Delta MLP exhibit promising accuracy in reproducing energy and forces, offering a cost-effective alternative for studying enzymatic reactions.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Bryant Kim, Ryan Snyder, Mulpuri Nagaraju, Yan Zhou, Pedro Ojeda-May, Seth Keeton, Mellisa Hege, Yihan Shao, Jingzhi Pu
Summary: The new method, RP-FM-CV, enables efficient AI/MM free energy simulations through mean force fitting in collective variables. Demonstrated on a solution-phase chemical reaction, this method accurately predicts free energy profiles by reproducing mean forces, showcasing its effectiveness in simulating chemical reactions in solution.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Bryant Kim, Yihan Shao, Jingzhi Pu
Summary: The study introduces a hybrid framework named dp-QM/MM method, which improves the response property of SE/MM methods through high-level molecular-polarizability fitting. Corrective polarizabilities generated through machine learning effectively reduce errors in solute molecular polarizability and bring simulated free energy profiles closer to experimental results.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Xiaoliang Pan, Richard Van, Evgeny Epifanovsky, Jian Liu, Jingzhi Pu, Kwangho Nam, Yihan Shao
Summary: This article proposes an improved multiple time step method to accelerate ai-QM/MM MD simulations of condensed-phase reactions, successfully achieving a significant reduction in computational time.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Ban Wang, Cristina Ascenzi Pettenuzzo, Jujhar Singh, Gavin E. Mccabe, Logan Clark, Ryan Young, Jingzhi Pu, Yongming Deng
Summary: Readily available and facilely tunable pyridine N-oxides have been developed as effective photoinduced hydrogen-atom-transfer (HAT) catalysts for site-selective C-H functionalizations. The pyridine N-oxide radicals generated from Noxides by photoredox catalyzed single-electron oxidation are the key intermediates for achieving alkylation, amination, azidation, allylation, and cyanation. The fine-tuning of reactivity and selectivity through operational simple structural modification shows promising capability for selective functionalization of unactivated C(sp(3))-H bonds.
Article
Chemistry, Multidisciplinary
Songyuan Yao, Richard Van, Xiaoliang Pan, Ji Hwan Park, Yuezhi Mao, Jingzhi Pu, Ye Mei, Yihan Shao
Summary: Inspired by recent work, this study investigates the possibility of deriving an implicit solvent model from explicit solvent molecular dynamics simulations using machine learning techniques. The authors successfully trained a machine learning potential for alanine dipeptide to capture its interactions with the average solvent environment configuration. The predicted forces and free energy surface were in good agreement with reference values, demonstrating the potential of machine learning-based implicit solvent models for ab initio-QM MD simulations.
Article
Chemistry, Multidisciplinary
Sumon Hati, Xuehui Yang, Prashant Gupta, Barry B. Muhoberac, Jingzhi Pu, Jing Zhang, Rajesh Sardar
Summary: This study reports the programmable manipulation of inorganic-organic interfacial electronic properties of ligand-functionalized plasmonic nanoparticles (NPs), which is crucial for their applications such as catalysis, photovoltaics, and biosensing. By functionalizing gold triangular nanoprisms (Au TNPs) with thiocinnamate ligands of varying surface dipole moments, the localized surface plasmon resonance (LSPR) properties of the Au TNPs in solid state can be reversibly tuned with a significant peak broadening. The shape of the NPs has a significant impact on the plasmonic response and work function modulation.
Article
Chemistry, Physical
Ryan Snyder, Bryant Kim, Xiaoliang Pan, Yihan Shao, Jingzhi Pu
Summary: In this study, a machine learning-facilitated approach is proposed to obtain free energy profiles matching high-accuracy quantum mechanical/molecular mechanical methods at a lower computational cost. The results show that this method significantly reduces energy errors and improves the accuracy of internal forces, bringing the predicted free energies closer to experimental benchmarks.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Xiaoliang Pan, Richard Van, Jingzhi Pu, Kwangho Nam, Yuezhi Mao, Yihan Shao
Summary: This study demonstrates that the contributions of individual residues to the reaction free energy and barrier can be obtained using postprocessed ai-QM/MM free energy simulation trajectories. The electrostatic, polarization, and van der Waals contributions from each residue to the free energy barrier can be determined through mean force integration along the minimum free energy pathway. The analysis procedure also allows for the assessment of contributions from different collective variables along the reaction coordinate.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Ryan Snyder, Bryant Kim, Xiaoliang Pan, Yihan Shao, Jingzhi Pu
Summary: In this work, a machine-learning-facilitated method is proposed to obtain AI/MM-quality free energy profiles through efficient SE/MM simulations. Gaussian process regression is used to learn the energy and force corrections. The effectiveness of this method is demonstrated on a reaction system and the results show closer agreement with AI/MM benchmarks and experimental results.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Sara A. Dille, Kyle J. Colston, Stephen C. Ratvasky, Jingzhi Pu, Partha Basu
Summary: A series of oxo-Mo(iv) complexes with fully oxidized and fully reduced dithiolene ligands have been synthesized and characterized. The oxidation states of coordinated dithiolene ligands are supported with spectral and crystallographic data, and the electronic structure of this system is probed by density functional theory (DFT) calculations.
Article
Chemistry, Physical
Xiaoliang Pan, Pengfei Li, Junming Ho, Jingzhi Pu, Ye Mei, Yihan Shao
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2019)